Ecdysterones from Rhaponticum carthamoides (Willd.) Iljin reduce hippocampal excitotoxic cell loss and upregulate mTOR signaling in rats
Abstract
Glutamate-induced excitotoxicity is a key pathological mechanism in many neurological disease states. Ecdysterones derived from Rhaponticum carthamoides (Willd.) Iljin (RCI) have been shown to alleviate glutamate-induced neuronal damage; although their mechanism of action is unclear, some data suggest that they enhance signaling in the mechanistic target of rapamycin (mTOR) signaling pathway. This study sought to elucidate the mechanisms underlying ecdysterone-mediated neuroprotection. We used in silico target prediction and simulation methods to identify putative ecdysterone binding targets, and to specifically identify those that represent nodes where several neurodegenerative diseases converge. We then used histological analyses in a rat hippocampal excitotoxicity model to test the effectiveness of ecdysterones in vivo. We found that RCI-derived ecdysterones should bind to glutamatergic NMDA-type receptors (NMDARs); specifically, in vivo modeling showed binding to the GRIN2B subunit of NMDARs, which was found also to be a node of convergence in several neurodegenerative disease pathways. Computerized network construction by using pathway information from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database showed putative links between GRIN2B and mTOR pathway elements including phosphoinositide-3kinase (PI3K), mTOR, and protein kinase C (PKC); these elements are associated with neuronal survival. Brain tissue western blots of ecdysterone-treated rats showed upregulated PI3K, Akt, mTOR, and phosphorylated Akt and mTOR, and down regulated GRIN2B and the apoptotic enzyme cleaved caspase-3. Ecdysterone treatment also prevented glutamate-induced rat hippocampal cell loss. In summary, RCI-derived ecdysterones appear to prevent glutamatergic excitotoxicity by increasing mTOR/Akt/PI3K signaling activity.
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The protective mechanism involved upregulation of PI3K, Akt, and mTOR and downregulation of cleaved caspase-3 and GRIN2B.
“The protective mechanism appeared via a similar mechanism as follows: the upregulation of PI3K, Akt, and mTOR and the downregulation of the apoptotic enzyme cleaved caspase-3 and GRIN2B, a glutamate NMDA receptor involved in rare neural development disorders.”
From Molecular Targets of 20-Hydroxyecdysone in Mammals, Mechanism of Action: Is It a Calorie Restriction Mimetic and Anti-Aging Compound? (2025) · cites this paper as [52]
Ecdysterones derived from Rhaponticum chartamides were preventive against glutamate-induced excitotoxicity in rat brains.
“Ecdysterones derived from Rhaponticum chartamides were also preventive against glutamate-induced excitotoxicity in rat brains [52].”
From Molecular Targets of 20-Hydroxyecdysone in Mammals, Mechanism of Action: Is It a Calorie Restriction Mimetic and Anti-Aging Compound? (2025) · cites this paper as [52]
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- Authors
- Wu, J., Gao, L., Shang, L., Wang, G., Wei, N., Chu, T., Chen, S., Zhang, Y., Huang, J., Wang, J., & Lin, R.
- Affiliations
- Shenyang Pharmaceutical University (CN)
- Shenyang Medical College (CN)
- Shihezi University (CN)
- Corresponding author
- Huang, Jian
- Wang, Jinhui
- ORCID
- Venue
- Fitoterapia
- Publisher
- Elsevier BV
- Published
- 2017-06
- Volume
- 119
- Pages
- 158-167
- ISSN
- 0367-326X (ISSN-L)
- OpenAlex
- W2602453218
- Cited by
- 25
- References
- 31
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 2 · 2023: 5 · 2022: 1 · 2021: 4 · 2020: 2 · 2018: 1
- FWCI
- 0.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Fitoterapia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (U1303124)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- 20-hydroxyecdysone, Rhaponticum carthamoides, glutamate excitotoxicity, hippocampal neuronal loss, neuroprotection, mTOR signaling, PI3K/Akt signaling, NMDA receptor, NR2B subunit, caspase-3, neurodegenerative diseases
- MeSH terms
- Animals, Ecdysterone, Hippocampus, Male, Phosphorylation, Molecular Structure, Signal Transduction, Up-Regulation, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Plant Roots, Neuroprotective Agents, Glutamic Acid, Leuzea, Proto-Oncogene Proteins c-akt, Rats, Caspase 3, Molecular Dynamics Simulation, TOR Serine-Threonine Kinases, Molecular Docking Simulation
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